Department of Urology, Urological Institute, Gansu Key Laboratory of Urinary System, Lanzhou University Second Hospital, Lanzhou, China.
Cancer Biother Radiopharm. 2020 Nov;35(9):661-672. doi: 10.1089/cbr.2019.3123. Epub 2020 Apr 9.
Prostate cancer (PCa) is the second most common cancer among men, threatening men's health and life. Long noncoding RNA Zinc-finger E-box binding homeobox 1 antisense gene 1 (ZEB1-AS1) and Cullin 4B (CUL4B) were reported to be connected with the tumorigenesis of PCa. However, it is unclear whether ZEB1-AS1 regulates the expression of CUL4B in PCa. The levels of ZEB1-AS1 and CUL4B in PCa tissues and cells were evaluated by quantitative real-time polymerase chain reaction. Protein levels of CUL4B, p21, CyclinD1, matrix metalloprotease 9 (MMP9), E-cadherin, phosphorylated-phosphatidylinositol 3 kinase (p-PI3K), PI3K phosphorylated protein kinase B (p-AKT), AKT, p-mTOR and mammalian target of rapamycin (mTOR) in PCa tissues or cells were assessed by Western blot analysis. The proliferation, migration, and invasion abilities of PCa cells were determined with 3-(4, 5-dimethylthiazol-2-YI)-2,5-diphenyltetrazolium bromide (MTT) or transwell assay. The interaction between ZEB1-AS1 or CUL4B and microRNA-342-3p (miR-342-3p) was predicted using starBase v2.0 database and confirmed by the dual-luciferase reporter assay. ZEB1-AS1 and CUL4B were upregulated and miR-342-3p was downregulated in PCa tissues and cells. Both ZEB1-AS1 and CUL4B inhibition constrained proliferation, migration, and invasion of PCa cells. Moreover, the elevation of CUL4B reversed the effects of ZEB1-AS1 silencing on the proliferation, migration, and invasion of PCa cells. Importantly, ZEB1-AS1 modulated CUL4B expression by sponging miR-342-3p in PCa cells. Besides, ZEB1-AS1 mediated PI3K/AKT/mTOR signal pathway by miR-342-3p/CUL4B axis in PCa cells. ZEB1-AS1 modulated PCa progression through mediating PI3K/AKT/mTOR signaling by miR-342-3p/CUL4B axis, providing a possible strategy for the treatment of PCa.
前列腺癌（PCa）是男性中第二常见的癌症，威胁着男性的健康和生命。长链非编码 RNA 锌指 E 框结合同源盒 1 反义基因 1（ZEB1-AS1）和 Cullin 4B（CUL4B）被报道与 PCa 的发生有关。然而，ZEB1-AS1 是否调节 PCa 中 CUL4B 的表达尚不清楚。通过定量实时聚合酶链反应评估 PCa 组织和细胞中的 ZEB1-AS1 和 CUL4B 水平。通过 Western blot 分析评估 PCa 组织或细胞中 CUL4B、p21、CyclinD1、基质金属蛋白酶 9（MMP9）、E-钙黏蛋白、磷酸化磷脂酰肌醇 3 激酶（p-PI3K）、PI3K 磷酸化蛋白激酶 B（p-AKT）、AKT、p-mTOR 和哺乳动物雷帕霉素靶蛋白（mTOR）的蛋白水平。通过 3-（4,5-二甲基噻唑-2-YI）-2,5-二苯基四氮唑溴盐（MTT）或 Transwell 测定评估 PCa 细胞的增殖、迁移和侵袭能力。使用 starBase v2.0 数据库预测 ZEB1-AS1 或 CUL4B 与 microRNA-342-3p（miR-342-3p）之间的相互作用，并通过双荧光素酶报告基因测定进行验证。ZEB1-AS1 和 CUL4B 在 PCa 组织和细胞中上调，miR-342-3p 下调。ZEB1-AS1 和 CUL4B 抑制均限制了 PCa 细胞的增殖、迁移和侵袭。此外，CUL4B 的升高逆转了 ZEB1-AS1 沉默对 PCa 细胞增殖、迁移和侵袭的影响。重要的是，ZEB1-AS1 通过在 PCa 细胞中海绵吸附 miR-342-3p 来调节 CUL4B 的表达。此外，ZEB1-AS1 通过 miR-342-3p/CUL4B 轴调节 PCa 细胞中的 PI3K/AKT/mTOR 信号通路。ZEB1-AS1 通过 miR-342-3p/CUL4B 轴调节 PI3K/AKT/mTOR 信号通路调节 PCa 进展，为 PCa 的治疗提供了一种可能的策略。
